Tue Oct 7 05:02:31 2014
Overview
Context
- Building on
SigFuge- per-gene analysis
- cluster by per-base expression
- extend per-gene clustering
- better annotations
- incorporate splicing
Connected Components
- joint work with Yin Hu, Jan Prins
- data driven annotations
- graphs: nodes (exons), edges (splice junctions)
- requires specifying parameters
thresh_junctionfilter_num_present_samples(8)thresh_junctionfilter_present_support(5)coverageThreshold_exon(.5)coverageThreshold_intron(10)
Connected Components
## gIdx gStart gStop kind start stop s1 s2 s3 ## 107 gene56 119793 119838 e 119793 119838 0.00 2.283 2.478 ## 108 gene57 119919 119953 e 119919 119953 1.00 3.771 2.743 ## 109 gene58 121312 179059 e 121312 121573 128.51 185.855 117.916 ## 110 gene58 121312 179059 j 121573 121961 95.00 249.000 32.000 ## 111 gene58 121312 179059 j 121573 123217 0.00 5.000 1.000 ## 112 gene58 121312 179059 e 121574 121960 10.32 27.439 8.796 ## 113 gene58 121312 179059 e 121961 122090 314.45 384.592 181.223 ## 114 gene58 121312 179059 j 122090 123217 354.00 335.000 23.000 ## 115 gene58 121312 179059 e 123217 123282 411.89 352.758 127.409 ## 116 gene58 121312 179059 j 123282 123386 301.00 277.000 136.000
LUSC chr9 Analysis
Lengths of connected components
Distribution of median exon expression
compute distribution of average expression over each exon and plot distributions grouped by the number of exons each gene
Location of single exon components
## [1] TRUE
…contrast with UCSC KnownGenes
…contrast with UCSC KnownGenes
- 845 overlaps
- overlap consisting of:
- 254 UCSC genes
- 830 connected components
Example of overlap
- Gene: SPATA31A5
- overlapped with 39 single exon connected components.
CDKN2A (p16/p14) locus
UCSC Genome Browser view
- ucsc browser for chr9:21,965,000-21,995,000
Connected components in region
Exon level expression for gene1791
…adding annotations
Genomic coordinates
Data Object
Data Object
- have only really looked at exon information
- also have coverage of junctions
- how to study?
- separately and aggregate?
- graph structure?
- example using
gene1791component
Standard PCA, exon expression
Standard PCA, exon expression
look at clusters
Standard PCA, exon expression
Standard PCA, junction coverage
Graph based approaches
Graph based approaches
## 15 x 15 sparse Matrix of class "dgCMatrix" ## ## [1,] 75 . 170 . . . . . . . . . . . . ## [2,] . 30 . . . . . . . . . . . . . ## [3,] . . 118 24 . . . . . . . . . . . ## [4,] . . . 24 6 . . 12 . . 3 . . . . ## [5,] . . . . 7 . . . . . . . . . . ## [6,] . . . . . 5 5 . . . . . . . . ## [7,] . . . . . . 12 2 . . 4 . . . . ## [8,] . . . . . . . 16 . . . . . . . ## [9,] . . . . . . . . . . . . . . . ## [10,] . . . . . . . . . 1 1 . . . . ## [11,] . . . . . . . . . . 17 . . 7 . ## [12,] . . . . . . . . . . . 61 37 . . ## [13,] . . . . . . . . . . . . 109 . . ## [14,] . . . . . . . . . . . . . 6 . ## [15,] . . . . . . . . . . . . . . 4
- example of an adjacency matrix for ONE sample
- 177 samples leads to a 3-dimensional tensor
- tensor factorizations
- spectral methods
Ongoing work
- understanding connected components better
- hard rules
- looking at mismatch density, multimapping, …
- developing suitable analysis methods
- clustering graph objects
- explore alternative formulations
R Environment
R Environment
Running time:
proc.time() - start_time ## user system elapsed ## 47.536 1.181 48.936
Compiled on:
Sys.time() ## [1] "2014-10-07 05:03:20 EDT"
R Environment
Session Information:
sessionInfo() ## R version 3.1.1 (2014-07-10) ## Platform: x86_64-apple-darwin13.3.0 (64-bit) ## ## locale: ## [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8 ## ## attached base packages: ## [1] grid parallel stats graphics grDevices utils datasets ## [8] methods base ## ## other attached packages: ## [1] rmarkdown_0.3.3 ## [2] mvnmle_0.1-11 ## [3] igraph_0.7.1 ## [4] PTAk_1.2-9 ## [5] tensor_1.5 ## [6] org.Hs.eg.db_2.14.0 ## [7] RSQLite_0.11.4 ## [8] DBI_0.3.1 ## [9] TxDb.Hsapiens.UCSC.hg19.knownGene_2.14.0 ## [10] BSgenome.Hsapiens.UCSC.hg19_1.3.1000 ## [11] annotate_1.42.1 ## [12] SplicingGraphs_1.4.1 ## [13] Rgraphviz_2.8.1 ## [14] graph_1.42.0 ## [15] GenomicAlignments_1.0.6 ## [16] BSgenome_1.32.0 ## [17] Rsamtools_1.16.1 ## [18] Biostrings_2.32.1 ## [19] XVector_0.4.0 ## [20] GenomicFeatures_1.16.3 ## [21] AnnotationDbi_1.26.1 ## [22] Biobase_2.24.0 ## [23] GenomicRanges_1.16.4 ## [24] GenomeInfoDb_1.0.2 ## [25] IRanges_1.22.10 ## [26] RColorBrewer_1.0-5 ## [27] ggbio_1.12.10 ## [28] BiocGenerics_0.10.0 ## [29] ggplot2_1.0.0 ## ## loaded via a namespace (and not attached): ## [1] acepack_1.3-3.3 base64enc_0.1-2 ## [3] BatchJobs_1.4 BBmisc_1.7 ## [5] BiocParallel_0.6.1 biomaRt_2.20.0 ## [7] biovizBase_1.12.3 bitops_1.0-6 ## [9] brew_1.0-6 caTools_1.17.1 ## [11] checkmate_1.4 cluster_1.15.3 ## [13] codetools_0.2-9 colorspace_1.2-4 ## [15] compiler_3.1.1 dichromat_2.0-0 ## [17] digest_0.6.4 evaluate_0.5.5 ## [19] fail_1.2 foreach_1.4.2 ## [21] foreign_0.8-61 formatR_1.0 ## [23] Formula_1.1-2 gridExtra_0.9.1 ## [25] gtable_0.1.2 Hmisc_3.14-5 ## [27] htmltools_0.2.6 iterators_1.0.7 ## [29] knitr_1.6 labeling_0.3 ## [31] lattice_0.20-29 latticeExtra_0.6-26 ## [33] MASS_7.3-35 Matrix_1.1-4 ## [35] munsell_0.4.2 nnet_7.3-8 ## [37] plyr_1.8.1 proto_0.3-10 ## [39] Rcpp_0.11.3 RCurl_1.95-4.3 ## [41] reshape2_1.4 rpart_4.1-8 ## [43] rtracklayer_1.24.2 scales_0.2.4 ## [45] sendmailR_1.2-1 splines_3.1.1 ## [47] stats4_3.1.1 stringr_0.6.2 ## [49] survival_2.37-7 tools_3.1.1 ## [51] VariantAnnotation_1.10.5 XML_3.98-1.1 ## [53] xtable_1.7-4 yaml_2.1.13 ## [55] zlibbioc_1.10.0